反应详情
EQUATION
反应方程式
REACTANTS
反应物
PRODUCTS
生成物
AUXILIARIES
试剂、催化剂与溶剂
CONDITIONS
反应条件
- 温度
- 10 °C
PROCEDURE
实验过程
1-[4-(2-Aminopyridin-4-yloxy)-2-fluorophenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester (176.0 kg), tetrahydrofuran (1876 kg), acetonitrile (692 kg) and pyridine (860 kg) were mixed and cooled to 10° C. Phenyl chloroformate (105 kg) was added dropwise to the mixed solution over a period of 1 hour at 10° C. The crystals were precipitated while the solution was added dropwise. After completing the dropwise addition, the completion of reaction was confirmed using an HPLC apparatus. Subsequently, acetonitrile (692 kg) was added to the reaction mixture. The crystals were collected by filtration, washed with a mixed solution of tetrahydrofuran (234 kg) and acetonitrile (207 kg) and dried under reduced pressure to give the crude crystals of 1-[2-fluoro-4-(2-phenoxycarbonylaminopyridin-4-yloxy)phenylcarbamoyl]cyclopropanecarboxylic acid benzyl ester (202. 9 kg). The crude crystals (202.9 kg), acetonitrile (638 kg) and water (812 L) were stirred for 1 hour at 20° C. The crystals were collected by filtration, washed with acetonitrile (319 kg) and dried under reduced pressure to give the title compound (174.8 kg). Apparent yield 77.1%, purity 93.9% (HPLC area percentage).
WORKUP
后处理
- customThe crystals were precipitated while the solution
- additionwas added dropwise
- additionthe dropwise addition
- customthe completion of reaction
- filtrationThe crystals were collected by filtration
- washwashed with a mixed solution of tetrahydrofuran (234 kg) and acetonitrile (207 kg)
- customdried under reduced pressure